tbuckley/cabot-search huggingface dataset:
Outpatient convalescent plasma therapy for high-risk patients with early COVID-19: a randomized placebo-controlled trial
Authors: Arvind Gharbharan, Carlijn Jordans, Lisa Zwaginga, Grigorios Papageorgiou, Nan van Geloven, Peter van Wijngaarden, Jan den Hollander, Faiz Karim, Elena van Leeuwen-Segarceanu, Robert Soetekouw, Jolanda Lammers, Douwe Postma, Linda Kampschreur, Geert Groeneveld, Francis Swaneveld, C. Ellen van der Schoot, Hannelore Götz, Bart Haagmans, Marion Koopmans, Susanne Bogers, Corine Geurtsvankessel, Jaap Jan Zwaginga, Casper Rokx, Bart Rijnders
Journal: Clinical Microbiology and Infection (2022)

The potential benefit of convalescent plasma (CP) therapy for coronavirus disease 2019 (COVID-19) is highest when administered early after symptom onset. Our objective was to determine the effectiveness of CP therapy in improving the disease course of COVID-19 among high-risk outpatients.A multicentre, double-blind randomized trial was conducted comparing 300 mL of CP with non-CP. Patients were ≥50 years, were symptomatic for <8 days, had confirmed RT-PCR or antigen test result for COVID-19 and had at least one risk factor for severe COVID-19. The primary endpoint was the highest score on a 5-point ordinal scale ranging from fully recovered (score = 1) or not (score = 2) on day 7, over hospital admission (score = 3), intensive care unit admission (score = 4) and death (score = 5) in the 28 days following randomization. Secondary endpoints were hospital admission, symptom duration and viral RNA excretion.After the enrolment of 421 patients and the transfusion in 416 patients, recruitment was discontinued when the countrywide vaccination uptake in those aged >50 years was 80%. Patients had a median age of 60 years, symptoms for 5 days, and 207 of 416 patients received CP therapy. During the 28 day follow-up, 28 patients were hospitalized and two died. The OR for an improved disease severity score with CP was 0.86 (95% credible interval, 0.59-1.22). The OR was 0.58 (95% CI, 0.33-1.02) for patients with ≤5 days of symptoms. The hazard ratio for hospital admission was 0.61 (95% CI, 0.28-1.34). No difference was found in viral RNA excretion or in the duration of symptoms.In patients with early COVID-19, CP therapy did not improve the 5-point disease severity score.
Comparative analysis of transmission and vaccine effectiveness in Omicron and Delta variant outbreaks in China
Authors: Kangguo Li, Feng Ruan, Zeyu Zhao, Zhinan Guo, Zimei Yang, Shanshan Yu, Buasiyamu Abudunaibi, Xuebao Zhang, Xiling Yin, Wenhua Mei, Tianmu Chen
Journal: Journal of Infection (2022)
Genomic profiling for clinical decision making in lymphoid neoplasms
Authors: Laurence de Leval, Ash A. Alizadeh, P. Leif Bergsagel, Elias Campo, Andrew Davies, Ahmet Dogan, Jude Fitzgibbon, Steven M. Horwitz, Ari M. Melnick, William G. Morice, Ryan D. Morin, Bertrand Nadel, Stefano A. Pileri, Richard Rosenquist, Davide Rossi, Itziar Salaverria, Christian Steidl, Steven P. Treon, Andrew D. Zelenetz, Ranjana H. Advani, Carl E. Allen, Stephen M. Ansell, Wing C. Chan, James R. Cook, Lucy B. Cook, Francesco d’Amore, Stefan Dirnhofer, Martin Dreyling, Kieron Dunleavy, Andrew L. Feldman, Falko Fend, Philippe Gaulard, Paolo Ghia, John G. Gribben, Olivier Hermine, Daniel J. Hodson, Eric D. Hsi, Giorgio Inghirami, Elaine S. Jaffe, Kennosuke Karube, Keisuke Kataoka, Wolfram Klapper, Won Seog Kim, Rebecca L. King, Young H. Ko, Ann S. LaCasce, Georg Lenz, José I. Martin-Subero, Miguel A. Piris, Stefania Pittaluga, Laura Pasqualucci, Leticia Quintanilla-Martinez, Scott J. Rodig, Andreas Rosenwald, Gilles A. Salles, Jesus San-Miguel, Kerry J. Savage, Laurie H. Sehn, Gianpietro Semenzato, Louis M. Staudt, Steven H. Swerdlow, Constantine S. Tam, Judith Trotman, Julie M. Vose, Oliver Weigert, Wyndham H. Wilson, Jane N. Winter, Catherine J. Wu, Pier L. Zinzani, Emanuele Zucca, Adam Bagg, David W. Scott
Journal: Blood (2022)
Impact of individual and treatment characteristics on wearable sensor-based digital biomarkers of opioid use
Authors: Brittany P. Chapman, Bhanu Teja Gullapalli, Tauhidur Rahman, David Smelson, Edward W. Boyer, Stephanie Carreiro
Journal: npj Digital Medicine (2022)

Opioid use disorder is one of the most pressing public health problems of our time. Mobile health tools, including wearable sensors, have great potential in this space, but have been underutilized. Of specific interest are digital biomarkers, or end-user generated physiologic or behavioral measurements that correlate with health or pathology. The current manuscript describes a longitudinal, observational study of adult patients receiving opioid analgesics for acute painful conditions. Participants in the study are monitored with a wrist-worn E4 sensor, during which time physiologic parameters (heart rate/variability, electrodermal activity, skin temperature, and accelerometry) are collected continuously. Opioid use events are recorded via electronic medical record and self-report. Three-hundred thirty-nine discreet dose opioid events from 36 participant are analyzed among 2070 h of sensor data. Fifty-one features are extracted from the data and initially compared pre- and post-opioid administration, and subsequently are used to generate machine learning models. Model performance is compared based on individual and treatment characteristics. The best performing machine learning model to detect opioid administration is a Channel-Temporal Attention-Temporal Convolutional Network (CTA-TCN) model using raw data from the wearable sensor. History of intravenous drug use is associated with better model performance, while middle age, and co-administration of non-narcotic analgesia or sedative drugs are associated with worse model performance. These characteristics may be candidate input features for future opioid detection model iterations. Once mature, this technology could provide clinicians with actionable data on opioid use patterns in real-world settings, and predictive analytics for early identification of opioid use disorder risk.
Long-Term Outcomes and Genetic Predictors of Response to Metastasis-Directed Therapy Versus Observation in Oligometastatic Prostate Cancer: Analysis of STOMP and ORIOLE Trials
Authors: Matthew P. Deek, Kim Van der Eecken, Philip Sutera, Rebecca A. Deek, Valérie Fonteyne, Adrianna A. Mendes, Karel Decaestecker, Ana Ponce Kiess, Nicolaas Lumen, Ryan Phillips, Aurélie De Bruycker, Mark Mishra, Zaker Rana, Jason Molitoris, Bieke Lambert, Louke Delrue, Hailun Wang, Kathryn Lowe, Sofie Verbeke, Jo Van Dorpe, Renée Bultijnck, Geert Villeirs, Kathia De Man, Filip Ameye, Daniel Y. Song, Theodore DeWeese, Channing J. Paller, Felix Y. Feng, Alexander Wyatt, Kenneth J. Pienta, Maximillian Diehn, Soren M. Bentzen, Steven Joniau, Friedl Vanhaverbeke, Gert De Meerleer, Emmanuel S. Antonarakis, Tamara L. Lotan, Alejandro Berlin, Shankar Siva, Piet Ost, Phuoc T. Tran
Journal: Journal of Clinical Oncology (2022)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co‐primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The initial STOMP and ORIOLE trial reports suggested that metastasis-directed therapy (MDT) in oligometastatic castration-sensitive prostate cancer (omCSPC) was associated with improved treatment outcomes. Here, we present long-term outcomes of MDT in omCSPC by pooling STOMP and ORIOLE and assess the ability of a high-risk mutational signature to risk stratify outcomes after MDT. The primary end point was progression-free survival (PFS) calculated using the Kaplan-Meier method. High-risk mutations were defined as pathogenic somatic mutations within ATM, BRCA1/ 2, Rb1, or TP53. The median follow-up for the whole group was 52.5 months. Median PFS was prolonged with MDT compared with observation (pooled hazard ratio [HR], 0.44; 95% CI, 0.29 to 0.66; P value &lt; .001), with the largest benefit of MDT in patients with a high-risk mutation (HR high-risk, 0.05; HR no high-risk, 0.42; P value for interaction: .12). Within the MDT cohort, the PFS was 13.4 months in those without a high-risk mutation, compared with 7.5 months in those with a high-risk mutation (HR, 0.53; 95% CI, 0.25 to 1.11; P = .09). Long-term outcomes from the only two randomized trials in omCSPC suggest a sustained clinical benefit to MDT over observation. A high-risk mutational signature may help risk stratify treatment outcomes after MDT.
Glycemic Variability Patterns Strongly Correlate With Partial Remission Status in Children With Newly Diagnosed Type 1 Diabetes
Authors: Olivier G. Pollé, Antoine Delfosse, Manon Martin, Jacques Louis, Inge Gies, Marieke den Brinker, Nicole Seret, Marie-Christine Lebrethon, Thierry Mouraux, Laurent Gatto, Philippe A. Lysy
Journal: Diabetes Care (2022)

To evaluate whether indexes of glycemic variability may overcome residual β-cell secretion estimates in the longitudinal evaluation of partial remission in a cohort of pediatric patients with new-onset type 1 diabetes.Values of residual β-cell secretion estimates, clinical parameters (e.g., HbA1c or insulin daily dose), and continuous glucose monitoring (CGM) from 78 pediatric patients with new-onset type 1 diabetes were longitudinally collected during 1 year and cross-sectionally compared. Circadian patterns of CGM metrics were characterized and correlated to remission status using an adjusted mixed-effects model. Patients were clustered based on 46 CGM metrics and clinical parameters and compared using nonparametric ANOVA.Study participants had a mean (± SD) age of 10.4 (± 3.6) years at diabetes onset, and 65% underwent partial remission at 3 months. β-Cell residual secretion estimates demonstrated weak-to-moderate correlations with clinical parameters and CGM metrics (r2 = 0.05-0.25; P < 0.05). However, CGM metrics strongly correlated with clinical parameters (r2 >0.52; P < 0.05) and were sufficient to distinguish remitters from nonremitters. Also, CGM metrics from remitters displayed specific early morning circadian patterns characterized by increased glycemic stability across days (within 63-140 mg/dL range) and decreased rate of grade II hypoglycemia (P < 0.0001) compared with nonremitters. Thorough CGM analysis allowed the identification of four novel glucotypes (P < 0.001) that segregate patients into subgroups and mirror the evolution of remission after diabetes onset.In our pediatric cohort, combination of CGM metrics and clinical parameters unraveled key clinical milestones of glucose homeostasis and remission status during the first year of type 1 diabetes.
Ordering of Laboratory Tests in a Teaching Hospital
Authors: Edward T. Wong
Journal: JAMA (1983)

A review of ordering patterns for thyroid function tests and for measurements of creatine kinase (CK) isoenzyme and lactate dehydrogenase (LDH) isoenzyme levels indicated considerable misuse. We employed an educational program for both types of tests, but changed the request form only for ordering the thyroid function tests. No changes were made in the forms for ordering CK and LDH isoenzyme tests. The effect was a prompt decrease in ordering triiodothyronine radioimmunoassay and thyrotropin tests to 38% and 61%, respectively, of baseline rates. There was no effect on rates of ordering CK and LDH isoenzyme tests, which were 102% and 96%, respectively, of baseline rates. The improved use of thyroid function tests was likely because of the change in the laboratory request form, since the educational strategy by itself had no effect on the ordering of CK and LDH isoenzyme tests. (<i>JAMA</i>1983;249:3076-3080)
The Presence and Accessibility of Firearms in the Homes of Adolescent Suicides
Authors: David A. Brent
Journal: JAMA (1991)

<h3>Objective.</h3> —The presence of guns in the home, the type of gun, and the method of storage were all hypothesized to be associated with risk for adolescent suicide. <h3>Design.</h3> —Case-control study. <h3>Subjects.</h3> —The case group consisted of 47 adolescent suicide victims. The two psychiatric inpatient control groups were 47 suicide attempters and 47 never-suicidal psychiatric controls, frequency-matched to the suicide victims on age, gender, and county of origin. <h3>Setting.</h3> —The cases were a consecutive community sample, whereas the inpatients were drawn from a university psychiatric hospital. <h3>Main Outcome Measure.</h3> —Odds of the presence of guns in the home of suicide victims (cases) relative to controls. <h3>Results.</h3> —Guns were twice as likely to be found in the homes of suicide victims as in the homes of attempters (adjusted odds ratio, 2.1; 95% confidence interval, 1.2 to 3.7) or psychiatric controls (adjusted odds ratio, 2.2; 95% confidence interval, 1.4 to 3.5). Handguns were not associated with suicide to any statistically significantly greater extent than long guns. There was no difference in the methods of storage of firearms among the three groups, so that even guns stored locked, or separate from ammunition, were associated with suicide by firearms. <h3>Conclusions.</h3> —The availability of guns in the home, independent of firearms type or method of storage, appears to increase the risk for suicide among adolescents. Physicians should make a clear and firm recommendation that firearms be removed from the homes of adolescents judged to be at suicidal risk. (<i>JAMA</i>. 1991;266:2989-2995)
Can we predict who will benefit from cognitive-behavioural therapy? A systematic review and meta-analysis of machine learning studies
Authors: Sandra Vieira, Xinyi Liang, Raquel Guiomar, Andrea Mechelli
Journal: Clinical Psychology Review (2022)

Cognitive-behavioural therapy (CBT) is the first line of treatment for several mental health disorders. However, not all patients show clinical improvements after receiving CBT. Machine learning allows inferences at the individual level and therefore is a promising approach for predicting who will and will not benefit from CBT. A comprehensive literature search was conducted to identify all studies that used machine learning to predict clinical response to CBT. A random-effects meta-analysis of proportions was used to estimate an overall performance accuracy across all studies. Twenty-four studies (N = 7497) were identified, covering five diagnostic groups: Major Depressive Disorder (k = 4), Obsessive-Compulsive Disorder (OCD, k = 5), Post-Traumatic Stress Disorder (k = 2), Anxiety Disorders (AD, k = 7), Substance Use Disorders (k = 4) and two transdiagnostic models. Studies used clinical, neuroimaging, cognitive and genetic data, or a combination of these, as predictors. The overall performance accuracy across studies was 74.0% [70.0–77.8]. Accuracies differed significantly between diagnostic groups and was highest in PTSD (78.7%, 69.1–87.0), AD (77.6%, 67.5–86.4) and OCD (76.1%, 67.3–84.0). Some studies were at a high risk of bias due to how the outcome was operationalised and/or how the analyses were conducted/reported. There are many challenges to overcome before these promising results can be applied to real-world clinical practice.
A Simple Cervicovaginal Epigenetic Test for Screening and Rapid Triage of Women With Suspected Endometrial Cancer: Validation in Several Cohort and Case/Control Sets
Authors: Chiara Herzog, Fátima Marín, Allison Jones, Iona Evans, Daniel Reisel, Elisa Redl, Lena Schreiberhuber, Sonia Paytubi, Beatriz Pelegrina, Álvaro Carmona, Paula Peremiquel-Trillas, Jon Frias-Gomez, Marta Pineda, Joan Brunet, Jordi Ponce, Xavier Matias-Guiu, Silvia de Sanjosé, Laia Alemany, Adeola Olaitan, Michael Wong, Davor Jurkovic, Emma J. Crosbie, Adam N. Rosenthal, Line Bjørge, Michal Zikan, Lukas Dostalek, David Cibula, Karin Sundström, Joakim Dillner, Laura Costas, Martin Widschwendter
Journal: Journal of Clinical Oncology (2022)

Endometrial cancer (EC) incidence has been rising over the past 10 years. Delays in diagnosis reduce survival and necessitate more aggressive treatment. We aimed to develop and validate a simple, noninvasive, and reliable triage test for EC to reduce the number of invasive diagnostic procedures and improve patient survival.We developed a test to screen and triage women with suspected EC using 726 cervical smear samples from women with and without EC, and validated the test in 562 cervicovaginal samples using three different collection methods (cervical smear: n = 248; vaginal swab: n = 63; and self-collection: n = 251) and four different settings (case/control: n = 388; cohort of women presenting with postmenopausal bleeding: n = 63; a cohort of high-risk women with Lynch syndrome: n = 25; and a nested case/control setting from a screening cohort and samples taken up to 3 years before EC diagnosis: n = 86).We describe the Women's cancer risk IDentification - quantitative polymerase chain reaction test for Endometrial Cancer (WID-qEC), a three-marker test that evaluates DNA methylation in gene regions of GYPC and ZSCAN12. In cervical, self-collected, and vaginal swab samples derived from symptomatic patients, it detected EC with sensitivities of 97.2% (95% CI, 90.2 to 99.7), 90.1% (83.6 to 94.6), and 100% (63.1 to 100), respectively, and specificities of 75.8% (63.6 to 85.5), 86.7% (79.3 to 92.2), and 89.1% (77.8 to 95.9), respectively. The WID-qEC identified 90.9% (95% CI, 70.8 to 98.9) of EC cases in samples predating diagnosis up to 1 year. Test performance was similar across menopausal status, age, stage, grade, ethnicity, and histology.The WID-qEC is a noninvasive reliable test for triage of women with symptoms suggestive of ECs. Because of the potential for self-collection, it could improve early diagnosis and reduce the reliance for in-person visits.
Perioperative Beta-Blocker Supply and Survival in Women With Epithelial Ovarian Cancer and a History of Cardiovascular Conditions
Authors: Katrina Spilsbury, Karen M. Tuesley, Sallie-Anne Pearson, Michael D. Coory, Peter Donovan, Christopher B. Steer, Louise M. Stewart, Nirmala Pandeya, Susan J. Jordan
Journal: Journal of Clinical Oncology (2022)

Surgery for epithelial ovarian cancer (EOC) may activate stress-inflammatory responses that stimulate tumor growth and increase metastatic growth. Animal and in vitro studies have shown that inhibition of the catecholamine-induced inflammatory response via beta-adrenergic receptor blockade has antitumor potential in EOC. However, observational studies have reported mixed results. We assessed whether beta-blocker (BB) use at the time of primary ovarian cancer surgery was associated with improved survival in a large population-based study.
The WHO-5 Well-Being Index: A Systematic Review of the Literature
Authors: Christian Winther Topp, Søren Dinesen Østergaard, Susan Søndergaard, Per Bech
Journal: Psychotherapy and Psychosomatics (2015)

Background: The 5-item World Health Organization Well-Being Index (WHO-5) is among the most widely used questionnaires assessing subjective psychological well-being. Since its first publication in 1998, the WHO-5 has been translated into more than 30 languages and has been used in research studies all over the world. We now provide a systematic review of the literature on the WHO-5. Methods: We conducted a systematic search for literature on the WHO-5 in PubMed and PsycINFO in accordance with the PRISMA guidelines. In our review of the identified articles, we focused particularly on the following aspects: (1) the clinimetric validity of the WHO-5; (2) the responsiveness/sensitivity of the WHO-5 in controlled clinical trials; (3) the potential of the WHO-5 as a screening tool for depression, and (4) the applicability of the WHO-5 across study fields. Results: A total of 213 articles met the predefined criteria for inclusion in the review. The review demonstrated that the WHO-5 has high clinimetric validity, can be used as an outcome measure balancing the wanted and unwanted effects of treatments, is a sensitive and specific screening tool for depression and its applicability across study fields is very high. Conclusions: The WHO-5 is a short questionnaire consisting of 5 simple and non-invasive questions, which tap into the subjective well-being of the respondents. The scale has adequate validity both as a screening tool for depression and as an outcome measure in clinical trials and has been applied successfully across a wide range of study fields.
Bifunctional Blockade: A Novel Immunotherapy Approach for Cervical Cancer
Authors: Kathryn M. Miller, Claire F. Friedman
Journal: Clinical Cancer Research (2022)

Summary SHR-1701, a bispecific fusion protein directed against PD-L1 and TGFβ, demonstrates promising clinical activity in advanced/recurrent cervical cancer. A recent study serves as a proof of principle that the TGFβ pathway may be successfully targeted, and that bispecific antibodies offer a novel therapeutic approach to do so. See related article by Feng et al., p. 5297
Congenital Malformations Following Chickenpox, Measles, Mumps, and Hepatitis
Authors: Morris Siegel
Journal: JAMA (1973)

The incidence of major malformations following maternal chickenpox, mumps, measles, and viral hepatitis was observed in a controlled, cohort study of offspring followed up until five years of age. Major congenital defects occurred in each viral group, but the malformations were equal in frequency and often similar in type to those observed among comparable controls for the respective viral groups. Consequently, the malformations that occurred could not be attributed directly to the associated diseases under study.
Nanomedicines targeting the inflammasome as a promising therapeutic approach for cell senescence
Authors: Swati Chaturvedi, Zaiba Naseem, Sherif F. El-Khamisy, Muhammad Wahajuddin
Journal: Seminars in Cancer Biology (2022)

Technological advancements in the present era have enhanced drug discovery and development. Nanomedicines are valuable pharmacotherapeutic tools against several diseases and disorders including aging related disorders. The mechanistic association between nanomedicines and molecular modulation have been investigated by many researchers. Notwithstanding the availability of tremendous amount of data, role of nanomedicines in aging related disorders intending inflammasome transfiguration have not been thoroughly reviewed till now. In the present review, we discuss the application of nanomedicines in aging related disorders. Further, we highlight the recent updates on modulated upstream and downstream signalling molecules of inflammasome cascade due to nanomedicines. The review will benefit researchers targeting nanomedicines as a therapeutic approach towards treatment age related disorders through inflammasome inflection.